Supplementation with sodium butyrate protects against antibiotic-induced increases in ethanol consumption behavior in mice

Alcohol. 2022 May:100:1-9. doi: 10.1016/j.alcohol.2021.12.003. Epub 2022 Jan 6.

Abstract

Background: We have recently reported that oral treatment of adult male C57BL/6J mice with a non-absorbable antibiotic cocktail resulted in an increase in ethanol intake and in significant reductions in butyrate-producing gut microbiota populations. This work led us to hypothesize that reduction in butyrate levels within the gut is linked to antibiotic-induced increases in voluntary ethanol consumption.

Objective: This study tested whether ad libitum sodium butyrate supplementation can prevent antibiotic-induced ethanol consumption in mice.

Methods: Sodium butyrate was provided to adult male C57BL/6J mice in drinking water alone or in combination with antibiotic cocktail. Effects on ethanol (20%) intake were measured using drinking in the dark and modified 2-bottle choice paradigms. Body parameters, food and liquid intake, cecum, and adipose tissues were measured during and/or at the conclusion of the drinking in the dark study. Cecal 16s rRNA was analyzed for microbiota diversity and changes in specific bacterial phyla/species.

Results: In drinking in the dark, sodium butyrate supplementation prevented antibiotic-induced increases in ethanol intake without altering basal ethanol consumption. Furthermore, sodium butyrate supplementation lowered ethanol preference in the 2-bottle choice study. Ethanol intake was correlated to specific bacterial phyla/species. Sodium butyrate did not affect the changes in microbiota diversity and composition induced by antibiotic cocktail.

Conclusions: The findings support a role of gut microbiota-derived butyrate in regulating alcohol-induced behaviors. Additionally, the work contributes to efforts in development of novel microbiome-based strategies as novel preventative and intervention-based therapeutics to address alcohol use disorder.

Keywords: antibiotic and sodium butyrate supplementation; ethanol intake and preference; gut microbiota diversity; gut-brain axis; short-chain fatty acids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents*
  • Butyric Acid / pharmacology
  • Dietary Supplements
  • Ethanol*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Ribosomal, 16S

Substances

  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S
  • Butyric Acid
  • Ethanol